With thanks to Professor Hannah Cock:
There have also been studies in over 3000 people with a range of different epilepsies taking CBD, with or without some THC, over periods of months to years, but without a blinded placebo arm (known as “Open studies”) . Open studies are often much less well designed, with a higher risk of more positive reports of effectiveness than might reflect the true situation. That doesn’t mean people in these studies are lying, just that epilepsy is inherently variable and will sometimes improve over time without a change in drugs, so by chance alone, this might sometimes be misinterpreted as a response to a new drug. There is also a lot of evidence for epilepsy that factors such as mood and stress can influence seizure frequency. Epilepsy trials, like trials in other conditions, show evidence of a placebo effect, and the placebo effect is known to be bigger where those taking what they think is a new drug have a strong belief that it will work. There has been intense social and media attention around cannabis in recent years. Together with a belief held by many that a natural product is inherently safer and more effective than a synthetic compound, this may mean a placebo effect is more likely with cannabis-derived drugs than some other new agents. Ultimately what this means is that observational data is useful in terms of detecting safety and side effects, but much less reliable as a measure of effectiveness.
Why the interest in cannabis?
The first good quality evidence appeared in 2016 , following which several well-controlled clinical trials of a near pure formulation of CBD (Epidiolex™, made by the UK Company GWPharma) were published [4-6]. EpidiolexTM contains less than 0.1% THC.The best trials of new drugs include a period of time when patients and their doctors don’t know if the additional drug they are taking as part of the trial contains the drug being studied or not. There are strict entry criteria so that after allocating people randomly into taking the drug or the placebo, the two groups are otherwise well-matched and the effect of the drug (as opposed to other factors) can be more clearly identified. These are called randomised blinded studies, and the pill or solution without the active drug is called the placebo. At the end of the blinded-placebo phase, everyone is then switched to the active drug. This is to measure the “placebo effect”: this refers to the known fact that some people will get better when they start a new pill or solution, even if it doesn’t’ actually contain the new drug under study. The blinded placebo-controlled studies of CBD have all been done in people with two particularly severe paediatric onsets, drug-resistant and often life-limiting epilepsies: Dravet’s syndrome and Lennox Gastaut Syndrome. Most of the participants were children, all taking other antiepileptic drugs at the same time, and having at least 8 disabling motor seizures each month. The blinded phase of the studies lasts only a few months, so has to include people with very frequent seizures to measure change.
The idea that cannabis might be helpful for some people with epilepsy has been around for thousands of years. However, it is only in the last few decades that we have started to understand why this might be. The brain makes chemicals (endocannabinoids) that are very similar in structure to some components of cannabis. These are involved in the regulation of how “excitable” the brain is, and so can also influence the liability to seizures. Cannabis contains hundreds of different chemicals, the two most important of which are Tetrahydrocannabidiol (THC) and Cannabidiol (CBD). Both THC and CBD seem to be effective against seizures . THC is the part that makes people feel “high”, but it can also cause negative effects such as anxiety and paranoia . THC has also been shown in some models of epilepsy to promote seizures. There is also a small risk of the brain getting used to THC, needing more over time (tolerance) and potentially leading to addiction. Taken regularly there is also significant evidence that THC, particularly in the developing brain (up to young adulthood), can sometimes cause permanent damage to IQ, mental health and brain structure. For these reasons, doctors and scientists have focussed on CBD, which doesn’t seem to carry these risks.
There have been no studies comparing CBD, or other cannabis-based drugs to other licensed drugs. In broad terms, based on the number of people whose seizures improve and the risk of side effects, CBD looks similar to other newer drugs. However, we have much more data about the safety and effectiveness of other drugs, especially taken in the long term, than we do about CBD. The possible benefits and risks of trying CBD in patients with drug-resistant epilepsies will vary considerably between individuals. Doctors specializing in epilepsy treatment will discuss this, and other treatment options, with patients and their families to help make the best decision for the individual.
Containing less than 0.1% THC, pure cannabidiol (CBD), has been prescribed in certain circumstances, and through clinical trials has been shown to be effective in complex epilepsies, more specifically Dravet syndrome and Lennox Gastaut syndrome. These findings have been submitted with a view to gaining a licence. There is no evidence about the efficacy or safety of higher amounts of THC.
The effects of cannabis on epilepsy have been under discussion for a number of years and the current interest in the case of Billy Caldwell has highlighted this even further.
Cannabis oils available in the UK and on the internet are not regulated medicines so their contents and dosage will not be consistent. People must always speak with their specialist epilepsy consultant if they are considering any alternative treatment including cannabis oil.
Cannabis has long been thought to have therapeutic properties. Cannabis products contain a substance called THC; the component that causes a medical high. In the UK there are laws regarding the amount of THC in cannabis products which are only legal if they contain less than 0.3% THC.
Elinor Ben-Menachem, professor of neurology and epilepsy at the University of Gothenburg’s Sahlgren Academy, said: “LGS and Dravet syndrome are two of the most severe and difficult-to-treat forms of childhood-onset epilepsy, with few patients achieving adequate seizure control. The EMA approval of Epidyolex will bring hope to patients and families, with the potential to better control seizures and improve quality of life.”
GW has also filed the drug for approval in Switzerland and Israel. It is conducting further clinical trials on the treatment of other forms of epilepsy with the medicine.
More than 150 patients have already been treated with the medicine in the UK under compassionate use or as part of an early access programme. “We know the families are desperate,” Tovey said.
Cambridge-based GW said the European Medicines Agency (EMA) and the European commission had approved Epidyolex for seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome (LGS) and Dravet syndrome for patients aged two years and older.
The approval means the medicine – a plant-derived, strawberry-flavoured cannabidiol oral solution that is taken twice a day and lacks the “high” associated with cannabis – can be launched across Europe. Up to 50,000 children and young adults in Europe have one of the two syndromes, including about 10,000 in the UK.
Isabella Brambilla, the chair of the Dravet Syndrome European Federation, said: “We are very happy that patients will now have access to a much-needed new treatment option, and one routed through a rigorous clinical trials programme and licensed by the EMA.”
The first cannabis-based medicine for childhood epilepsy is expected to be available soon in the UK and the rest of Europe after its UK manufacturer, GW Pharmaceuticals, received the green light from European authorities.